An accurate coarse-grained model for chitosan polysaccharides in aqueous solution.

Computational models can provide detailed information about molecular conformations and interactions in solution, which is currently inaccessible by other means in many cases. Here we describe an efficient and precise coarse-grained model for long polysaccharides in aqueous solution at different physico-chemical conditions such as pH and ionic strength. The Model is carefully constructed based on all-atom simulations of small saccharides and metadynamics sampling of the dihedral angles in the glycosidic links, which represent the most flexible degrees of freedom of the polysaccharides. The model is validated against experimental data for Chitosan molecules in solution with various degree of deacetylation, and is shown to closely reproduce the available experimental data. For long polymers, subtle differences of the free energy maps of the glycosidic links are found to significantly affect the measurable polymer properties. Therefore, for titratable monomers the free energy maps of the corresponding links are updated according to the current charge of the monomers. We then characterize the microscopic and mesoscopic structural properties of large chitosan polysaccharides in solution for a wide range of solvent pH and ionic strength, and investigate the effect of polymer length and degree and pattern of deacetylation on the polymer properties.

Properties of Poloxamer Molecules and Poloxamer Micelles Dissolved in Water and Next to Lipid Bilayers: Results from Computer Simulations.

To study the properties of poloxamer molecules P85 and P188 and micelles containing these poloxamers in bulk water and also next to lipid bilayers, we performed coarse-grained molecular dynamics computer simulations. We used MARTINI force-field and adjusted Lennard-Jones nonbonded interaction strength parameters for poloxamer beads to take into account the presence of polarizable water. Simulations of systems containing poloxamer molecules or micelles solvated in bulk water showed that structural properties, such as radii of gyration of the molecules and micelles, agree with the ones inferred from experiments. We observed that P85 micelle is almost spherical in shape, whereas the P188 micelle is distorted from being spherical. Simulations containing systems with the water-lipid bilayer interface showed that hydrophilic blocks of poloxamers interact with lipid headgroups of the bilayer and remain at the interface, whereas hydrophobic blocks prefer to insert into the central hydrophobic region of the bilayer. Simulations containing poloxamer micelles next to lipid bilayer showed no permeation of these micelles into the bilayer. To study the "healing" properties of P188 poloxamer, we performed simulations on a system containing a P188 micelle next to "damaged" lipid bilayer containing a pore. We observed that hydrophobic chains of poloxamers got inserted into the bilayer through the pore region, ultimately closing the pore.